by Centre for Eye Research Australia

Intravitreal delivery of AAV2.7m8 achieves strong transduction of mice photoreceptors. Credit: Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2408345121

Australian scientists have successfully used an innovative gene therapy technique in the lab to combat a key cause of vision loss in “wet” age-related macular degeneration and diabetic eye disease.

Their research, published in the Proceedings of the National Academy of Sciences, highlights the potential of gene therapy to provide a new alternative treatment to regular eye injections.

The pre-clinical research was led by Satheesh Kumar and Associate Professor Guei-Sheung (Rick) Liu from the Center for Eye Research Australia (CERA) and University of Melbourne, along with scientists from the University of Sydney, Children’s Medical Research Institute, University of Western Australia and Zhongshan City People’s Hospital, China.

The researchers for the first time used an RNA editing tool—known as CRISPR Cas13—to suppress the production of Vascular Endothelial Growth Factor (VEGF) in human retinal cells.

VEGF is a protein that causes abnormal leaky blood vessels to grow in the retina at the back of the eye—and is the key driver of vision loss in diseases such as “wet” age-related macular degeneration and diabetic retinopathy that affect 200 million people worldwide.

Associate Professor Liu said the new research demonstrated the potential to develop a gene therapy using CRISPR Cas13 to control VEGF in the retina.

“Our study shows the potential of RNA editing to develop gene therapies that offer an alternative treatment to the invasive, frequent eye injections that are currently used to treat wet macular degeneration and diabetic eye disease,”‘ he said.

The experiment targeted the mRNA sequence that instructs cells to produce VEGF. It delivered the RNA editing tool via an AAV viral vector and was tested on a mouse model and human retinal cells derived from stem cells.

It showed that the viral vector was effective in delivering the treatment to retinal cells and produced a significant reduction in VEGF, and a slowing of disease progression in the mouse model.

Satheesh Kumar said this research informs future work to develop a more tailored approach to delivering gene therapies to patients.

“RNA editing enables us to change the genetic instructions that influence the way cells behave without permanently altering their DNA,”‘ he said. “This could allow treatments to be adjusted over time, depending on clinical need.”

Associate Professor Liu said the research aims to make a difference for people with eye disease who face the prospect of having eye injections every six to 12 weeks for the rest of their lives.

“Although this research is in the early discovery stages and requires further development before transitioning to clinical trials, we envision that RNA editing could become a viable alternative to invasive and costly eye injections that have become a fact of life for many people living with wet macular degeneration or diabetic eye disease.”‘

More information: Satheesh Kumar et al, Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2408345121

Journal information:Proceedings of the National Academy of Sciences

Provided by Centre for Eye Research Australia